Weight self-stigma, the internalization of negative societal stereotypes, is a problem amongst populations with high weight. Weight self-stigma is associated with psychological inflexibility and maladaptive health-related behaviors. In this study, we explore how weight-related psychological inflexibility may influence weight self-stigma and health-related outcomes in 79 adults with high weight. Participants were primarily white (92.4%) and female (82.3%), with an average age of 39.56 and average body mass index of 33.78. The present study uses baseline, self-report data from a larger trial. Results indicate that weight self-stigma was negatively correlated with maladaptive eating behaviors, weight, and mental health. Weight-related psychological inflexibility was found as a significant mediator for the relationship between weight self-stigma and emotional eating, sedentary behavior, and mental health. Weight-related psychological inflexibility did not mediate the relationships between weight self-stigma and other eating measures and physical activity. These results support targeting weight-related psychological inflexibility and weight self-stigma in interventions.